tbuckley/cabot-search huggingface dataset:
QOL-19. Post-Intensive-Care Syndrome – pediatric (PICS-p) among patients with brain tumors – therapeutic strategies and preventive recommendations
Authors: Justyna Korzeniewska
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Patients with brain tumors needed in intensive care unit (ICU) stay due to tumors symptoms or neurosurgery, experience a complex of physical, psychological, and cognitive symptoms. This constellation of signs and symptoms has been named Post-Intensive-Care Syndrome – pediatric (PICS-p). An interesting problem emerging from this research and requires a deeper exploration are the differences between PICS-p symptoms and primary tumors effects or side effects of treatment e.g. irradiation. METHOD: Psychological repeated testing and long-term observation was performed in 350 childhood brain tumor survivors (various types and localizations of tumor) to determine PICS-p symptoms. Age at psychological diagnosis ranged from 6 to 20 years. Full psychological outcome included assessment of psychophysical, cognitive and affective problems. The patients were examined using battery of neuropsychological methods and psychological interview. Analysis of medical history was also performed. The next level of the study was distinguished between PICS-p symptoms and the effects of tumor localization and oncology treatment, including radiotherapy. RESULTS: In our sample patients presents low scores in the all PICS-p domains: physical, cognitive and mental. Low level of motor skills, impairing daily living activities are characteristic. In this group lower IQ scores, poorer visual motor integration, learning disabilities, memory and language problems persisted. Typical problems in mental area are depressive symptoms, anxiety with intrusive memories, emotional and behavioural disruptions, socialization problems with significantly low level of social contacts. CONCLUSIONS: The results of this study suggest that PICS-p well describes and explains the psychosocial problems of these patients. It allows prepare an individual psychological interventions and rehabilitative program for particular patient as well as therapeutic strategies for whole group of patients. Draft recommendations for diagnosis of PICS-p specific for patients with brain tumors, risk factors and preventive procedures will be presented and discussed.
LGG-03. Pediatric spinal deformities concomitant with spinal cord pilocytic astrocytoma
Authors: Monika Kapitancuke, Vilma Rutkauskaite, Rimantas Zagorskis, Giedrius Bernotavicius, Ona Lapteva, Jelena Rascon
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Childhood spinal cord tumours may lead to spinal deformity. Rapid scoliosis progression, a left thoracic curve and early onset scoliosis are associated with an increased risk of intraspinal anomalies, therefore magnetic resonance imaging (MRI) should be performed. CASE PRESENTATION: A 1-year-old girl presented with progressive early onset scoliosis. MRI of the spine showed diffuse intramedullary lesion at vertebral level T5 – T11 and abnormal curvature of the thoracic spine to the right – 39-degree Cobb angle, after a few moths – 71-degree. Blood and cerebrospinal fluid examination ruled out a neuroinfection and autoimmune diseases. Histology revealed BRAF V600E-mutant pilocytic astrocytoma (PA) (IDH non-mutant), DNA methylation profiling – PA, MGMT promoter methylation – not detected, SNP-A karyotyping – normal. Treatment with weekly vinblastin was started due to non-operable tumour and progressive scoliosis. Spinal deformity was managed using serial casting with only mild correction of curvature. In the second case report, a 14-year-old boy either presented with progressive scoliosis. Spine x-ray showed abnormal curvature of the thoracic spine to the left - 89-degree Cobb angle and after a few years - 120-degree. MRI of the spine detected intramedullary tumour masses located at vertebral level T3-T5. Surgical resection revealed BRAF V600E-mutant PA (IDH, ATRX, TERT non-mutant), DNA methylation profiling – PA, MGMT promoter status – not methylated, SNP-A karyotyping – non-specific trisomy of chromosome 5. The patient was followed-up by routine spine MRI. However, after 8 months new spinal cord masses appeared. It was decided to correct scoliosis only after the total tumour removal. CONCLUSIONS: Intramedullary spinal tumours are overall rare in the pediatric population. Of these, PA accounts for the majority, however treatment remains challenging. BRAF V600E mutation has relatively high frequency in PA. This mutation identification opens more treatment options such as targeted therapy with BRAF V600E and MEK inhibitors for progressive disease.
Comparison of tumor registry reporting and gastrointestinal oncologist determination of intrahepatic cholangiocarcinomas: A quality review analysis.
Authors: Alexander Raufi, Emma Safran, Rimini Breakstone, Khaldoun Almhanna
Journal: Journal of Clinical Oncology (2022)

e16113 Background: Diagnosing cholangiocarcinoma (CCA) can be challenging and these tumors are often misclassified as adenocarcinomas of unknown primary (AUP). Accurate identification is critically important to determine the true incidence and to understand the epidemiology of these cancers. Methods: As a quality assessment, gastrointestinal oncologists at our institution reviewed the tumor registry records of all patients diagnosed with intrahepatic CCA, extrahepatic CCA, hepatocellular carcinoma, adenocarcinoma of unknown primary, and adenocarcinoma not otherwise specified. Mixed hepatocellular/cholangiocarcinoma was excluded. Results: Initially the tumor registry reported 37 cases of intrahepatic CCA at the Lifespan Cancer Institute/Rhode Island Hospital between 2017-2020. However, review of the registry records by gastrointestinal oncologists revealed 10 additional cases of intrahepatic cholangiocarcinoma. These cases had been entered into the tumor registry with diagnosis codes of liver adenocarcinoma NOS (n = 8), liver cancer (n = 1) and liver NOS (n = 1). Following review, a total of 47 cases of intrahepatic CCA and 59 cases of extrahepatic CCA were identified at our institution between 2017-2020. The mean age of intrahepatic CCA was 58 and 48% were women. The mean age of extrahepatic CCA was 73 and 42% were women. The updated numbers were reported to the state tumor registry. Conclusions: Difficulties in diagnosis of cholangiocarcinoma may underestimate the true incidence of this disease in the United States. Careful review of tumor registry data across the United States would likely reveal large discrepancies between actual and reported incidence of this disease and further study is warranted.
Characteristics of patients with myelofibrosis on ruxolitinib for three or more years.
Authors: Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Helen T. Chifotides, Lingsha Zhou, Zeev Estrov, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2022)

e19082 Background: Ruxolitinib (RUX) was the first JAK1/2 inhibitor approved for patients with advanced phase of myelofibrosis (MF) with median therapy duration of about 3 years. We aimed to characterize clinical features of patients treated with RUX for ≥3 years who presented to our institution between January 2000 and January 2019. Methods: Retrospective review of medical records of 131 patients who received RUX for ≥3 years. Clinical characteristics, therapy details and overall survival (OS; Kaplan Meier method) were assessed at/from the time of RUX initiation. Cox proportional hazard model was used for univariate (known clinical variables) and multivariate analysis (p &lt; 0.05 on previous analysis) of factors associated with OS. Results: Median age of patients was 67 years (range, 31-84), 56% were males (clinical characteristics in Table). Among 62 patients with ≥ 28 gene next generation sequencing; 19, 24 and 19 patients had none, 1 and ≥2 mutations beyond JAK2, MPL, CALR, respectively. Eighty four percent of patients received RUX as frontline therapy. Median time to RUX from presentation and from MF was 4 (range, 0.1-123) and 11 months (range, 0.1-228), respectively. Starting dose of RUX was ≥ 15 mg, 10 mg and 5 mg twice daily in 110 (84%), 17 (13%), and 4 (3%) patients, respectively. Median duration of RUX therapy was 76 months (95% CI, 56-88). At the time of last follow-up (median duration of 104 months; 95% CI, 93-115), 44 patients (35%) were on RUX. Reasons for discontinuation in the remaining patients included MF progression (n = 54; 62%), blastic phase (n = 7; 8%), cytopenias (n = 4; 5%) and unrelated causes (n = 22, 25%). Median OS since therapy start was 90 months (95% CI, 76-104) with 40% of patients being alive at 10 years. Patients ≥ 65 years had median OS of 76 months (95% CI, 67-85). Patients with intermediate 2 (n = 81) or high risk (n = 29) DIPSS at RUX start had median OS of 89 (95% CI, 71-107) and 72 (95% CI, 55-89) months, respectively. Factors affecting OS on univariate analysis (HR, 95% CI, p-value) were age &gt; 65 years (2.56, 1.49-4.35, &lt; 0.001), neutrophils % (0.97, 0.95-0.99, 0.006), blasts % (1.213, 1.035-1.421, 0.017), performance status of &lt;2 (0.228, 0.069-0.752, 0.015). The only factors retaining significance on multivariate analysis were age &gt; 65 years (2.7, 1.50-4.14, &lt; 0.001) and neutrophils % (0.66, 0.29- 0.86, 0.012). Conclusions: Forty percent of patients who remained on RUX for ≥3 years were alive at 10 years since their therapy initiation. Age remains the major predictive factor of survival despite long RUX therapy.[Table: see text]
LGG-28. Rapid symptomatic improvement for a patient treated with BRAF inhibition for BRAFV600E mutated ganglioglioma
Authors: Evan Cantor, Anne Cochrane, Stephanie Morris, Ashley Meyer, Andrea Ogle, Margaret Shatara, Andrew Cluster, Mai Deng, Mohamed S Abdelbaki, Nicole M Brossier
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Biologically targeted agents such as the BRAF inhibitor dabrafenib are now used to treat progressive low-grade glioma (LGG), but the effect of these agents on the neurologic symptoms that accompany LGGs is poorly understood. CASE: A 21-year-old male was diagnosed with medullary ganglioglioma (GG) after presenting with persistent vertigo and positional headaches. Immunohistochemistry was consistent with BRAF V600E mutation and dabrafenib was started. The patient had resolution of his neurologic symptoms within 3 weeks of treatment initiation; surveillance MRI several months later demonstrated interval decrease in tumor size. The patient remained on therapy for 2 years. Several days after planned drug discontinuation the patient had re-emergence of persistent vertigo that impaired his ability to work. Repeat imaging two months later demonstrated an increase in tumor size and solid enhancement along tumor margins. He was restarted on dabrafenib. Within one week, he again had complete resolution of his vertigo. DISCUSSION: Gangliogliomas are comprised of mixed neuronal and glial components and associated with epilepsy, headache and other localizing neurologic symptoms. In this report, we describe clinical and radiographic response from single-therapy dabrafenib in a patient with BRAF V600E+ GG, along with a very rapid resolution of neurologic symptoms upon initiation of the drug and recrudescence shortly following cessation of therapy. The symptoms subsided within a week of restarting dabrafenib, suggesting a separate, more rapid mechanism of symptom reversal than decline in tumor size. BRAF mutations have been identified in both the neuronal and glial components of ganglioglioma, suggesting that dabrafenib may provide symptomatic relief via inhibition of abberant neuronal processes. CONCLUSION: BRAF inhibitors can rapidly improve neurological symptoms via a rapid, not yet fully elucidated mechanism. Kinetics of this response suggest it is independent of effects on tumor volume and the degree of compression to tissue surrounding the tumor.
Association of the KRAS genotype and clinicopathologic findings of resected non–small cell lung cancer.
Authors: Yuko Oya, Katsuhiro Masago, Hirokazu Matsushita, Hiroaki Kuroda
Journal: Journal of Clinical Oncology (2022)

8545 Background: This study assessed the clinicopathological background of early-stage KRAS-mutated non-small-cell lung cancer and analyzed the biological process of KRAS-mutated tumor using an RNA sequencing procedure. Methods: We used a cohort of consecutive series of 179 surgically resected early-stage non-small-cell lung cancers harboring KRASmutations and analyzed the clinicopathological features, including the KRAS genotypes, affecting the recurrence-free survival and prognosis. Consequently, we performed RNA sequencing to determine the gene expression profiles of nineteen KRAS-mutated non-small-cell cancers. Results: The most common KRAS genotype was p.G12C (57; 31.8%). A high p-stage (hazard ratio [HR], 4.181; P &lt; 0.0001) and solid predominant adenocarcinoma histology (HR, 2.343; P = 0.0076) were significant independent prognostic factors for the recurrence-free survival. A high p-stage (HR, 3.793; P &lt; 0.0001), solid predominant adenocarcinoma histology (HR, 2.373; P = 0.0147), and KRAS p.G12V genotype (HR, 1.975; P = 0.0407) were significant independent prognostic factors for the overall survival. A gene expression analysis of the two factors revealed the p.G12V genotype to be closer to those of stem cells, and the traits of e an enhanced fatty acid and amino acid metabolism as well as a solid predominant phenotype were shown to an acquired a trait that can withstand hypoxia and the effect of prostaglandin-endoperoxide synthase Conclusions: The KRAS p.G12V genotype and solid predominant adenocarcinoma phenotype may be independent predictive factors of a poor clinical course in resected early-stage non-small-cell lung cancers, possibly due to the differentiation tendency observed in stem cells, the trait of an enhanced fatty acid and amino acid metabolism, and the effect of prostaglandin-endoperoxide synthase.
Clinical analysis of patients (pts) with Lung cancer treated with anti-PD1/PDL1 therapy.
Authors: Kaihua Tian, Xintong Wang
Journal: Journal of Clinical Oncology (2022)

e20522 Background: Characterization of Lung cancer treated with anti-PD1/PDL1 therapy was an approach to predict the clinical benefit. this research is a prospective and observational study of long-term immunization therapy safety in routine clinical practice in lung cancer. Methods: This study obtained 395 Chinese patients lung cancer patients who underwent surgical resection or biopsies from January 2020 to January 2022. It is aimed to evaluated the value of TMB,MSI,and PD-1 expression in the pts subset that was therapy at anti-PD1/PDL1 therapy(n = 47),other anticancer therapies (n = 348) included chemoradiation therapy(55%), docetaxel(18%), EGFR-TKIs (16%), pemetrexed (5%) etc. Results: In this cohort, lung cancer pts treated with anti-PD1/PDL1 therapy had a higher proportion of MSI-H than others (7.7% vs 3.4%). PD-L1 High expression in two groups (anti-PD1/PDL1 therapy vs others) about in 19.1%(n = 9) vs 10.6% (n = 37), and low expression in 8.9% (n = 31) vs 10.6% (n = 5) pts. Median TMB was 13 mut/Mb from anti-PD1/PDL1 therapy and 9.6 mut/Mb from other therapy. Conclusions: Lung cancer pts were integrated after immunotherapy vs other therapy, most pts received multiple subsequent anticancer therapies. In this study, immune-related biomarker analysis of lung cancer populations with multiple treatment methods may help improve the efficacy of precise treatment in lung cancer.[Table: see text]
Surgical management of complex renal tumors treated with robotic partial nephrectomy: From the planning to the intraoperative navigation via 3D virtual models
Authors: A. Pecoraro, F. Piramide, P. Verri, E. Checcucci, S. De Cillis, A. Piana, M. Manfredi, C. Fiori, F. Porpiglia, D. Amparore
Journal: European Urology (2022)
Extended duration of anti-PD-1 therapy, using reduced frequency dosing, in patients with advanced melanoma and Merkel cell carcinoma.
Authors: Lisa May Ling Tachiki, Karly Williams Silva, Daniel S Hippe, Dane Fritzsche, Aleksandra Raczka, Andrea Perdue, Julia Majovski, Alexandra Spallone, Daniel A Goldstein, Paul Nghiem, John A. Thompson, Evan Thomas Hall, Shailender Bhatia
Journal: Journal of Clinical Oncology (2022)

2588 Background: Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in patients with metastatic melanoma (Mel) and Merkel cell carcinoma (MCC) is unclear. ICI discontinuation in Mel patients, especially those without CR, may be associated with a higher rate of progression over time, as compared to ICI continuation. Thus, extending DoT could improve outcomes. However, indefinite continuation at standard frequency doses (SFD) is not logistically or financially viable. Based on data from phase I studies suggesting sustained PD-1 receptor occupancy beyond 3 months after a single dose of nivolumab, we employed reduced frequency dosing (RFD) of anti-PD-1 antibodies every 2-3 months, to extend ICI duration beyond 2 years. Methods: This retrospective study analyzes patients in our skin cancer clinic with metastatic Mel and MCC who experienced initial clinical benefit with anti-PD-1 administered at SFD and then transitioned to RFD. We analyzed safety and efficacy endpoints including progression free survival (PFS) and rates of immune-related adverse events (irAE) with RFD. We also compared the pharmaceutical costs and patient-centered costs between 2 years of treatment at SFD versus extended DoT at RFD. Results: From 2014 – 2021, 23 patients with either metastatic Mel (N = 18) or MCC (N = 5) received anti-PD-1 therapy at RFD. Median DoT at SFD in this cohort was 1.1 years (range 0.2 – 2.2) with best objective tumor responses of CR (N =6), PR (N = 11), SD (N = 6). Median DoT at RFD was 1.2 years (range 0.2 – 3.5). The median follow-up for the entire cohort is 3.7 years (range 0.7 – 6.3) after ICI initiation. The 3-year PFS in Mel patients was 100% in those with CR (3/3), 89% with PR (8/9), and 50% with SD (3/6). The 3-year PFS in MCC was 100% in all 5 patients, including patients with CR (3/3) and with PR (2/2). Any-grade irAEs occurred in 43% of patients by 3 years on RFD, and grade 3/4 irAEs presented in 15%. Among the subset of 15 patients with DoT &gt;2 years (median 3.4 yr, range 2.0 – 5.0), total savings amounted to $1.1 million in drugs costs and 384 hours of clinic and travel time despite the increased DoT, as compared to the calculated values for 2-year DoT at SFD. Conclusions: RFD may provide an alternative approach to extending DoT in patients receiving ICI without additional logistical and financial burden, while preserving outcomes. Efficacy and safety data suggest sustained biologic activity of ICI with RFD administration. PK/PD analyses on patient samples are ongoing to further characterize the RFD approach. The RFD approach could be utilized to expand ICI access to communities with limited healthcare resources, thereby impacting cancer outcomes at a global scale.
OTHR-23. Development of a cerebrospinal fluid liquid biopsy platform in pediatric patients with central nervous system tumors
Authors: Katrina O’Halloran, Dejerianne Ostrow, Eirini Christodoulou, Moiz Bootwalla, Venkata Yellapantula, Nicholas Chapman, Peter Chiarelli, Jason Chu, Mark Krieger, Xiaowu Gai, Jaclyn Biegel
Journal: Neuro-Oncology (2022)

Abstract Pediatric central nervous system (CNS) tumors carry high morbidity and mortality. The advent of targeted agents is aiming to change that through individualized, less invasive, and real-time molecular profiling. We successfully developed a cerebrospinal fluid (CSF) liquid biopsy (LB) platform combining low-pass whole genome sequencing (WGS) and targeted mutation and gene fusion analysis of cell-free (cf) DNA. WGS libraries were constructed with the xGen Prism DNA Library Prep Kit using 5ng of input cfDNA and paired-end sequenced (Illumina NextSeq 500) for an average 0.5x coverage across the genome. Copy number (CN) profiles were analyzed using the ichorCNA R package and compared with CN abnormalities of the primary tumors detected with CytoScanHD or Oncoscan arrays. Selected cases were analyzed for mutations or gene fusions using a custom glioma hybrid capture-based panel (Twist Bioscience) sequenced to 500-1000x across targeted regions. Mutations identified in LBs were compared with primary tumor OncoKids NGS panel results. CSF LBs from 44 tumor cases and 15 non-tumor controls were analyzed. Sixteen primary tumors had copy number changes, 10 had cfDNA detected in the LB across various primary tumor diagnoses (AT/RT, diffuse midline glioma, ependymoma, high-grade glioma, medulloblastoma, pilocytic astrocytoma). Four primary tumors had sequence alterations from the custom panel, two with detectable cfDNA (diffuse midline glioma H3K27M variant allele frequency (VAF) 49% and low-grade glioma BRAFV600E VAF 1.7%). Three patients had TP53 variants detected, all ultimately germline. Controls were negative across WGS and hybrid gene capture. Tumor DNA is detectable by both WGS and hybrid gene capture. Various histologic subtypes are detectable including embryonal and glioneuronal. CSF seems more enriched for cfDNA in high grade versus low grade tumors. These data suggest that NGS-based LB assays may be used to monitor pediatric patients with a variety of CNS tumors, from diagnosis through treatment and recurrence.
Focal therapy of index lesion with irreversible electroporation: Oncological and functional results at 30 months
Authors: B. Miñana López, G. De Andrés Boville, G. Barbas Bernardos, F. Villacampa Aubá, F. Ramón De Fata Chillón, L. Labairu Huerta, M. Torres Roca, C. Gutiérrez Castañé, J. Colombás Vives, S. Chiva Sanromán, J.E. Robles García, F. Díez-Caballero Alonso
Journal: European Urology (2022)
The best benefit population treated with lenvatinib plus anti-PD-1 for unresectable hepatocellular carcinoma.
Authors: Xiujuan Chang, Shumin Yu, Jianzhi Pang, Wei Zhang, Huifang Kong, Jiagan Huang, Guojie Zhang, Huixin Zhang, Yueyue Gu, Jihai Zhang, Zheng Dong, Yan Chen, Bin Yang, Jingping Liu, Yongping Yang, Zhen Zeng
Journal: Journal of Clinical Oncology (2022)

e16152 Background: To assess the efficacy and safety of lenvatinib plus anti-PD-1 versus lenvatinib alone in patients with unresectable hepatocellular carcinoma (u-HCC) and explore the characteristics of the benefit population for combination therapy. Methods: This retrospective study included 70 u-HCC patients that were treated with lenvatinib plus anti-PD-1 and 140 patients treated with lenvatinib alone in Fifth Medical Center of Chinese PLA General Hospital and Electric Power Hospital of Beijing from November 2017 to February 2021. Clinical features were balanced by stabilized inverse probability of treatment weighting (SIPTW). The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Subpopulation treatment effect pattern plot (STEPP) revealed differential treatment effects. The safety was evaluated by Common Terminology Criteria for AEs version 5.0. Results: During the median follow-up of 21.6 months, 120 (57%) patients died. The combination group showed better OS (21.4 vs. 14 months, p = 0.041), PFS (8.0 vs. 6.3 months, p = 0.015), ORR (38.6% vs. 22.9%, p = 0.026), and DCR (85.7% vs. 69.3%, p = 0.016) than the monotherapy group in unadjusted cohort, which was similar to SIPTW adjusted cohort. The two groups had comparable and manageable AEs. Macrovascular invasion (MVI, HR 2.6, 95%CI 2.18 - 3.92), extrahepatic spread (EHS, HR 2.16, 95%CI 1.49 - 3.13), and Child-Pugh B (CPB, HR 2.08, 95%CI 1.45 - 2.99) were independent factors of OS. Combination therapy improved the 12-month survival rate by 38% for patients with MVI or EHS and CPB, and by up to 18% in the other population. Conclusions: In conclusion, lenvatinib plus anti-PD-1 showed a favorable efficacy and controllable safety for u-HCC patients in real-world practice. The absolute improvement of the 12-month survival rate with combination therapy was more substantial in patients with major vascular invasion or extrahepatic spread and Child-Pugh B.